Description: Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta (PIK3CD), mRNA. RefSeq Summary (NM_005026): Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]. Transcript (Including UTRs) Position: hg19 chr1:9,711,790-9,789,172 Size: 77,383 Total Exon Count: 24 Strand: + Coding Region Position: hg19 chr1:9,770,514-9,787,104 Size: 16,591 Coding Exon Count: 22
ID:PK3CD_HUMAN DESCRIPTION: RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Short=PI3-kinase subunit delta; Short=PI3K-delta; Short=PI3Kdelta; Short=PtdIns-3-kinase subunit delta; EC=2.7.1.153; AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta; Short=PtdIns-3-kinase subunit p110-delta; Short=p110delta; FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity. CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. ENZYME REGULATION: Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells. PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. SUBUNIT: Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS (By similarity). Interacts with HRAS. SUBCELLULAR LOCATION: Cytoplasm. TISSUE SPECIFICITY: Isoform 2 is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform 1 and isoform 2 are widely expressed. Isoform 1 is expressed predominantly in leukocytes. PTM: Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity. MISCELLANEOUS: IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response. Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy (PubMed:20940048; PubMed:17290298). SIMILARITY: Belongs to the PI3/PI4-kinase family. SIMILARITY: Contains 1 C2 PI3K-type domain. SIMILARITY: Contains 1 PI3K-ABD domain. SIMILARITY: Contains 1 PI3K-RBD domain. SIMILARITY: Contains 1 PI3K/PI4K domain. SIMILARITY: Contains 1 PIK helical domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O00329
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Protein O00329 (Reactome details) participates in the following event(s):
R-HSA-508247 Gab2 binds the p85 subunit of Class 1A PI3 kinases R-HSA-879917 CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated R-HSA-914182 14-3-3 zeta binding allows recruitment of PI3K R-HSA-912629 CBL is tyrosine phosphorylated R-HSA-2045911 BCAP Signalosome phosphorylates PI(4,5)P2 forming PI(3,4,5)P3 R-HSA-2076220 CD19 Signalosome phosphorylates PI(4,5)P2 forming PI(3,4,5)P3 R-HSA-1676109 PI4P is phosphorylated to PI(3,4)P2 by PI3K3C[2] at the plasma membrane R-HSA-1676048 PI(4,5)P2 is phosphorylated to PI(3,4,5)P3 by PIK3C[1] at the plasma membrane R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3 R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-912526 Interleukin receptor SHC signaling R-HSA-912631 Regulation of signaling by CBL R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling R-HSA-8853659 RET signaling R-HSA-983705 Signaling by the B Cell Receptor (BCR) R-HSA-451927 Interleukin-2 family signaling R-HSA-449147 Signaling by Interleukins R-HSA-422475 Axon guidance R-HSA-1660499 Synthesis of PIPs at the plasma membrane R-HSA-1280218 Adaptive Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-1266738 Developmental Biology R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1483255 PI Metabolism R-HSA-168256 Immune System R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-9006925 Intracellular signaling by second messengers R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-1483257 Phospholipid metabolism R-HSA-5663202 Diseases of signal transduction R-HSA-162582 Signal Transduction R-HSA-556833 Metabolism of lipids R-HSA-1643685 Disease R-HSA-1430728 Metabolism
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